The supplies of liquid blood are currently limited by storage systems used in conventional blood storage practice. Using current systems, stored blood expires after a period of about 42 days of refrigerated storage at a temperature above freezing (i.e., 4° C.) as packed blood cell preparations. Expired blood cannot be used and must be discarded because it will harm the ultimate recipient. One of the primary reasons for blood spoilage is its continued metabolic activity after it is stored. For example, in 2007, more than 45 million units of packed red blood cells (pRBC) were collected and stored globally (15.6 million in US). During refrigerated storage, all of these pRBC became progressively damaged by storage lesions. When transfused within the current 6-week limit, stored pRBC have lower quality (fraction of pRBC removed; compromised O2 delivery capacity) as well as potential toxicity, often manifested as side effects of transfusion therapy. These storage lesions are observed as altered biochemical and physical parameters associated with stored cells. Examples of these in vitro measured parameters include reduced metabolite levels (ATP and 2,3-DPG), reduced surface area, echinocytosis, phosphatidylserine exposure, and reduced deformability.
Human red blood cells (RBC) in vivo are in a dynamic state. In whole blood, white blood cells are normally present in the range between 4,300 and 10,800 cells/μL and the normal RBC range at sea level is 5.4 million/μL (+0.8) for men and 4.8 million μL (+0.6) for women. The red blood cells contain hemoglobin, the iron-containing protein that carries oxygen throughout the body and gives red blood its color.
Stored blood undergoes steady deterioration which is partly caused by hemolysis, hemoglobin degradation and reduced adensine triphosphate (ATP) concentration that occur during the storage period. These reasons and others limit the amount of readily available high quality blood needed for transfusions.
When pRBC are stored at 1-6° C. (standard storage condition) in a blood storage bag, away from mechanical stress and the constantly cycling environment of the circulation, the senescence process is partially suspended. However, with the lack of constant nutrient replenishment and waste removal under refrigerated storage, pRBC are gradually damaged, resulting in compromised physiological functions. The following problems occur during extended storage:                a. When pRBC are stored for an extended period, storage lesions accumulate and deteriorate pRBC and cause the up to 1% of pRBC to be hemolyzed during storage and up to 25% to be removed shortly after transfusion.        b. Non-viable pRBC cause iron overload in chronically transfused patients.        c. Transfusion does not always achieve the intended outcome of increased tissue perfusion.                    Hemoglobin in pRBC do not release oxygen efficiently at tissues due to loss of 2,3-DPG.            pRBC are not able to enter and perfuse capillary beds due to loss of deformability.Transfusing pRBC stored for longer periods may result in higher morbidity and longer hospital stays compared to transfusing “fresher” red cells.                        
Higher morbidity and longer hospital stays result with pRBC that are stored longer than 2-3 weeks, in comparison to fresher red cells. For example, negative clinical outcomes in cardiac surgery occur when using ‘older’ blood; multiple organ failure in surgical patients reflecting the age of transfused red cells; correlation between older units and increased mortality in severe sepsis; failure to improve O2 utilization attributed to decreased 2,3-DPG and decreased cardiac index associated with increased blood viscosity
This evidence suggests that the ineffectiveness and negative consequences of transfusion is attributable at least in part to the compromising effects of extended storage of pRBC. In addition to immediate removal by the recipient of certain pRBC, consequences of pRBC storage lesions include: (i) Depletion of ATP (loss of RBC's ability to dilate the pre-capillary arteriole); (ii) Depletion of 2,3-DPG; (iii) Accumulation of oxidative damage caused by reactive oxygen species (ROS) formed by the reaction of denatured hemoglobin with O2; and (iv) Decreased pRBC deformability and increased pRBC viscosity—caused in part by oxidative damage to membrane and cytoskeleton. Less deformable pRBC are excluded from capillary channels resulting in low capillary occupancy and reduced tissue perfusion. Massive transfusion of undeformable cells may also contribute to multiple organ failure by blocking the organs' capillary beds. After transfusion, 2,3-DPG is synthesized relatively quickly in vivo to ˜50% of the normal level in as little as 7 hours and to ˜95% of the normal level in 2-3 days. However, since 2,3-DPG-depleted cells do not recover their levels immediately, O2-carrying capacity is compromised to the detriment of critically ill patients requiring immediate O2 delivery and tissue perfusion. There are numerous reports that emphasize the importance of pRBC with high oxygen carrying capacity in such clinical situations.
Packed red blood cells (pRBC) prepared from whole blood or from apheresis techniques currently undergo sequential processing to deplete plasma, leukocytes and oxygen. This results in increased processing time and loss of red blood cells.
The present disclosure overcomes the disadvantages of the conventional sequential processing of red blood cells via the development of a filter device that combines all three depletion steps into a single integrated device.